CARDIOVASCULAR

In this section we will provide scientific studies that are related to the ingredients contained in NMS Neuromuscular Support that deal with the cardiovascular system. This is additional information that we feel relates to the efficacy of this amazing product and should also give you an idea of the breadth and scope of the information about the ingredients in the NMS Formula dealing with health conditions other than Pain & Inflammation.

CARDIOVASCULAR --- THIAMINE

Congest Heart Fail. 2007 Jul-Aug;13(4):244-7
Loop diuretic therapy, thiamine balance, and heart failure.
Sica DA.
Section of Clinical Pharmacology and Hypertension, Division of Nephrology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0160, USA. dsica@mcvh-vcu.edu

Thiamine, or vitamin B1, is a water-soluble B complex vitamin that was first discovered in 1910 in the process of exploring how rice bran cured patients of beriberi. Thiamine is not synthesized in humans, therefore its availability for necessary cellular processes hinges on its continual ingestion. The amount of thiamine one needs to ingest to maintain balance is disease state-dependent or medication-dependent. Severe chronic thiamine deficiency can have significant neurologic and cardiac effects, the latter is reflected in a particular type of heart failure called wet beriberi. This form of heart failure clearly benefits from thiamine supplementation. It is unclear, however, whether thiamine supplementation offers any benefit in other forms of heart failure. Despite this, it is not unreasonable for heart failure patients to routinely ingest a thiamine-containing multivitamin; patients using diuretics have an increased urinary excretion of thiamine and thus are at a higher risk for developing thiamine deficiency. The role of thiamine in heart failure, however, remains arguable.

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Nutr Rev. 2000 Oct;58(10):319-23
Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition?
Suter PM, Vetter W.
Medical Policlinic, University Hospital, Z�rich, Switzerland.

Despite modern pharmacologic agents in the therapy of heart failure, the prevalence of heart failure is increasing worldwide. In the vitamin B1 deficiency disease beriberi, cardiac symptoms may represent the central feature. Two new studies confirmed that all diuretics lead to increased urinary thiamin excretion depending on the urinary flow rate. In a subject at risk, such as an elderly patient, chronic diuretic treatment may lead to a subclinical thiamin deficiency. Whether subclinical thiamin nutriture is a modulator of the prevalence and/or severity of heart failure is not known; however, it seems to be plausible from the metabolic point of view.

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Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H394-401. Epub 2007 Mar 16.
Abolition of reperfusion-induced arrhythmias in hearts from thiamine-deficient rats.
Oliveira FA, Guatimosim S, Castro CH, Galan DT, Lauton-Santos S, Ribeiro AM, Almeida AP, Cruz JS.
Department of Biochemistry and Immunology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, MG, CEP 31900-901, Brazil.

Extensive work has been done regarding the impact of thiamine deprivation on the nervous system. In cardiac tissue, chronic thiamine deficiency is described to cause changes in the myocardium that can be associated with arrhythmias. However, compared with the brain, very little is known about the effects of thiamine deficiency on the heart. Thus this study was undertaken to explore whether thiamine deprivation has a role in cardiac arrhythmogenesis. We examined hearts isolated from thiamine-deprived and control rats. We measured heart rate, diastolic and systolic tension, and contraction and relaxation rates. Whole cell voltage clamp was performed in rat isolated cardiac myocytes to measure L-type Ca(2+) current. In addition, we investigated the global intracellular calcium transients by using confocal microscopy in the line-scan mode. The hearts from thiamine-deficient rats did not degenerate into ventricular fibrillation during 30 min of reperfusion after 15 min of coronary occlusion. The antiarrhythmogenic effects were characterized by the arrhythmia severity index. Our results suggest that hearts from thiamine-deficient rats did not experience irreversible arrhythmias. There was no change in L-type Ca(2+) current density. Inactivation kinetics of this current in Ca(2+)-buffered cells was retarded in thiamine-deficient cardiac myocytes. The global Ca(2+) release was significantly reduced in thiamine-deficient cardiac myocytes. The amplitude of caffeine-releasable Ca(2+) was lower in thiamine-deficient myocytes. In summary, we have found that thiamine deprivation attenuates the incidence and severity of postischemic arrhythmias, possibly through a mechanism involving a decrease in global Ca(2+) release.

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Heart Fail Rev. 2006 Mar;11(1):75-82.
The management of conditioned nutritional requirements in heart failure.
Allard ML, Jeejeebhoy KN, Sole MJ.
Division of Cardiology, University Health Network, Toronto, Ontario.

Patients suffering from congestive heart failure exhibit impaired myocardial energy production, myocyte calcium overload and increased oxidative stress. Nutritional factors known to be important for myocardial energy production, calcium homeostasis and the reduction of oxidative stress, such as thiamine, riboflavin, pyridoxine, L-carnitine, coenzyme Q10, creatine and taurine are reduced in this patient population. Furthermore, deficiencies of taurine, carnitine, and thiamine are established primary causes of dilated cardiomyopathy.Studies in animals and limited trials in humans have shown that dietary replacement of some of these compounds in heart failure can significantly restore depleted levels and may result in improvement in myocardial structure and function as well as exercise capacity. Larger scale studies examining micronutrient depletion in heart failure patients, and the benefits of dietary replacement need to be performed. At the present time, it is our belief that these conditioned nutritional requirements, if unsatisfied, contribute to myocyte dysfunction and loss; thus, restoration of nutritional deficiencies should be part of the overall therapeutic strategy for patients with congestive heart failure.

CARDIOVASCULAR --- VITAMIN B6

Nutrition. 2006 Nov-Dec;22(11-12):1146-51. Epub 2006 Oct 10.
Low pyridoxal 5'-phosphate is associated with increased risk of coronary artery disease.
Lin PT, Cheng CH, Liaw YP, Lee BJ, Lee TW, Huang YC. School of Nutrition, Chung Shan Medical University, Taichung, Taiwan.

OBJECTIVE: The purpose of this study was to investigate the association between plasma pyridoxal 5'-phosphate (PLP) status and lipid profiles and to estimate the relation to the risk of coronary artery disease (CAD). METHODS: Patients who were identified by cardiac catheterization as having > or =70% stenosis of one major coronary artery were assigned to the case group (n = 184). The control group (n = 516) was comprised of healthy individuals with normal blood biochemical values. Plasma PLP, homocysteine, high-sensitivity C-reactive protein, lipid profiles (total cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triacylglycerol) were determined. RESULTS: Subjects with a plasma PLP level <30 nmol/L exhibited a significantly increased risk of CAD compared with subjects with a plasma PLP level > or =30 nmol/L (odds ratio, 1.85; 95% confidence interval, 1.16-2.95) after adjusting for homocysteine and high-sensitivity C-reactive protein. The association between PLP and the risk of CAD remained significant after each lipid profile was additionally adjusted. In addition, the combined presence of low PLP level and an abnormal lipid level increased the risk of CAD to an even greater degree. CONCLUSIONS: A borderline vitamin B6 deficiency (plasma PLP concentration <30 nmol/L) is strongly associated with the risk of CAD. The combined presence of low PLP and abnormal lipid levels increased the risk of CAD even further.

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Br J Nutr. 2006 Jun;95(6):1088-93.
Antioxidant activity of vitamin B6 delays homocysteine-induced atherosclerosis in rats.
Endo N, Nishiyama K, Otsuka A, Kanouchi H, Taga M, Oka T.
Department of Veterinary Physiology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.

Elevated plasma homocysteine is a risk factor for atherosclerotic disease. In the present study, we have examined whether the oxidative stress due to a low level of vitamin B6 accelerates the development of homocysteine-induced atherosclerosis in rats. First, the effect of homocysteine thiolactone intake (50 mg/kg per d) on vascular integrity, lipid peroxide concentration, endothelial NO synthase (eNOS) expression and biochemical profiles was examined at day 1, day 21 and day 42 (five rats per group). The histochemical staining of the rat aorta showed no change at day 1 and day 21, but the subendothelial space was observed to be enlarged in rat aorta at day 42 with exposure to homocysteine thiolactone. Expression of eNOS was observed in rat aorta at day 42, but not at day 1 and day 21. Serum lipid peroxide concentration and biochemical profiles including glucose cholesterol and triacylglycerol showed no change at any day. Second, the effect of homocysteine thiolactone intake in the presence and absence of vitamin B6 on vascular integrity was examined at day 1 and day 14 (five rats per group). Aortic lesions were observed in vitamin B6-deficient rat aorta at day 14 but not in vitamin B6-supplemented rats. The expression of eNOS was also observed in vitamin B6-deficient rat aorta at day 14. Serum lipid concentrations of the vitamin B6-deficient group significantly increased compared with concentrations of the vitamin B6-supplemented group, though serum concentration of homocysteine did not change between both groups. These results suggest that the oxidative stress caused by a low level of vitamin

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Am J Clin Nutr. 2004 Jun;79(6):992-8.
Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk.
Friso S, Girelli D, Martinelli N, Olivieri O, Lotto V, Bozzini C, Pizzolo F, Faccini G, Beltrame F, Corrocher R.
Department of Clinical and Experimental Medicine,University of Verona School of Medicine, Verona, Italy. simonetta.friso@univr.it

BACKGROUND: Low concentrations of pyridoxal-5'-phosphate (PLP), the active metabolite of vitamin B-6, are associated with high C-reactive protein (CRP) concentrations. Both low PLP and elevated inflammatory markers, such as high-sensitivity CRP (hs-CRP) and fibrinogen, are related to higher risk of coronary artery disease (CAD). OBJECTIVES: The objectives were to evaluate the relation between PLP and acute-phase reactants in affecting CAD risk and to estimate the risk of CAD related to low plasma PLP, either alone or in combination with high concentrations of acute-phase reactants and other classic risk factors for CAD. DESIGN: A case-control study was conducted with 742 participants: 475 with severe multivessel CAD and 267 free from coronary atherosclerosis (CAD-free). We measured plasma PLP, fibrinogen, hs-CRP, and serum lipid concentrations and all major biochemical CAD risk factors, including total homocysteine. RESULTS: A significant, inverse, graded relation was observed between PLP and both hs-CRP and fibrinogen (P < 0.001). The prevalence of PLP concentrations in the lower half of the population (<50th percentile: 36.3 nmol/L) was significantly higher among CAD patients than among CAD-free subjects (P < 0.001). The odds ratio for CAD risk related to low PLP concentrations after adjustments for the major classic CAD risk factors, including hs-CRP and fibrinogen, was 1.89 (95% CI: 1.18, 3.03; P = 0.008). The CAD risk as a result of low PLP was additive when considered in combination with elevated hs-CRP concentrations or with an increased ratio of LDL to HDL. CONCLUSION: Low plasma PLP concentrations are inversely related to major markers of inflammation and independently associated with increased CAD risk.

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CARDIOVASCULAR --- CURCUMIN

Biochem Pharmacol. 2008 Feb 15;75(4):787-809. Epub 2007 Aug 19

Curcumin as "Curecumin": from kitchen to clinic.
Goel A, Kunnumakkara AB, Aggarwal BB.

Gastrointestinal Cancer Research Laboratory, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, United States.

Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

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